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Journal of Integrative Medicine ›› 2014, Vol. 12 ›› Issue (5): 417-424.doi: 10.1016/S2095-4964(14)60040-6

• Research Article • Previous Articles     Next Articles

Electroacupuncture at Feishu (BL13) and Zusanli (ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease

Xin-fang Zhanga, Ji Zhub, Wen-ye Gengc, Shu-jun Zhaoa, Chuan-wei Jianga, Sheng-rong Caia, Miao Chengd, Chuan-yun Zhoud, Zi-bing Liua,d   

  1. Department of Physiology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China
    The Third Clinical College of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
    Department of Pharmacology, Shanghai Medical College of Fudan University, Shanghai 200032, China
    Institute of Acupuncture and Meridian, College of Acupuncture and Osteology, Anhui University of Chinese Medicine, Hefei 230038, Anhui Province, China
  • Received:2014-01-29 Accepted:2014-05-19 Online:2014-09-10 Published:2014-09-15

Objective

Inflammation and lung function decline are the main pathophysiological features of chronic obstructive pulmonary disease (COPD). Acupuncture can improve lung function in patients with COPD, but the underlying mechanisms are not well understood. Orexins (OXs), which are found in peripheral plasma, are neuropeptides that regulate respiration and their levels are related to COPD. Therefore, we hypothesized that acupuncture might alter OXs, reduce lung inflammation and improve lung function in COPD.

Methods

COPD was induced in rats by exposure to cigarette smoke for 8 weeks and injecting with lipopolysaccharide twice. Electroacupuncture (EA) was performed at Feishu (BL13) and Zusanli (ST36) for 30 min/d for 2 weeks. Rat lung function and morphology were assessed after EA. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) and orexin A and B levels in the lung tissue were detected by enzyme-linked immunosorbent assay. OX receptor mRNA levels and immunopositive cells were assessed with real-time polymerase chain reaction and immunohistochemical methods, respectively. The relationships among lung function, cell factors, and OX levels were analyzed by Pearson correlation analyses. 

Results

Compared with the control group, lung function was significantly decreased in the rats with COPD (P<0.05). There were obvious increases in TNF-α and IL-1β levels in BALF (P<0.05 and P<0.01, respectively), orexin A level in lung tissue (P<0.01; but not orexin B) and mRNA expressions of OX 1 type receptor (OXR1) and OX 2 type receptor (OXR2) in lung tissue (P<0.05 and P<0.01, respectively); the integrative optical densities (IODs) of both receptors were greater in the COPD group (P<0.05). For rats with COPD subjected to EA, lung function was improved (P<0.05). There were notable decreases in TNF-α and IL-1β levels (P<0.05 and <0.01, respectively) in BALF. Orexin A, but not orexin B, levels in lung tissue also decreased (P<0.01), as did mRNA expression of OX1R and OX2R in lung tissue (P<0.05 and P<0.01, respectively). Receptor IODs were also reduced after EA treatment (P<0.05). Furthermore, orexin A levels and ratio of forced expiratory volume in 0.3 s to forced vital capacity were strongly negatively correlated (P<0.01), and orexin A was positively correlated with TNF-α and IL-1β (P<0.001 and P<0.05, respectively).

Conclusion

EA at Zusanli and Feishu improved lung function of rats with COPD and had an anti-inflammatory effect, which may be related to down-regulation of OXA and its receptors.

Key words: Pulmonary disease, Chronic obstructive, Electroacupuncture, Point BL13 (Feishu), Point ST36 (Zusanli), Orexin, Anti-inflammation, Rats

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Figure 1

Comparison of lung histology in different groupsA: Hematoxylin-eosin staining showed large lung alveoli and thin alveolar septum in the control and EA groups, but small lung alveoli and thickened alveolar septum in the COPD group. B: The histogram showed the total area ratio of lung alveolus to alveolar septum (A/t). Data in Figure 1B are expressed as mean ± standard deviation (n=6). *P<0.05, vs control group. EA: electroacupuncture; COPD: chronic obstructive pulmonary disease."

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Figure 2

Orexin receptor expression in rat lung A-F: Immunohistochemical staining showing immunoreactive cells (arrows) for orexin 1 type receptor (OX1R) and orexin 2 type receptor (OX2R) in the lung of the control (A and D), COPD (B and E) and EA group (C and F) rats. Bar, 100 μm. G: Comparison of the integrative optical density (IOD) of OX1R or OX2R. H: Comparison of OX1R and OX2R mRNA levels. Data in Figure 2G and Figure 2H are expressed as mean±standard deviation and analyzed by one-way analysis of variance followed by least-significant difference t tests for comparison of means between two groups (n=6). *P<0.05, vs control group; △P<0.05, vs COPD group. EA: electroacupuncture; COPD: chronic obstructive pulmonary disease."

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